Straehl P, Galeazzi R L, Soliva M
Clin Pharmacol Ther. 1984 Oct;36(4):485-92. doi: 10.1038/clpt.1984.208.
Isosorbide 5-mononitrate (IS-5-MN) and isosorbide 2-mononitrate (IS-2-MN) kinetics were studied in two groups of young healthy subjects after intravenous injection of 5 mg of both and after oral doses of 20 mg of IS-2-MN and 10, 15, and 20 mg of IS-5-MN. Mononitrate plasma levels were measured by GLC with capillary columns. After intravenous injection, IS-5-MN and IS-2-MN plasma levels declined biexponentially and could be described by an open two-compartment body model. Distribution t 1/2 was rapid; 8.6 min for IS-5-MN and 12.5 min for IS-2-MN. Substances were distributed throughout body water; volume of distribution at steady state (Vd ss) was 48 l for IS-5-MN and 55 l for IS-2-MN and elimination t 1/2 was 4.15 hr for IS-5-MN and 1.9 hr for IS-2-MN. Total plasma clearance was 8.5 l/hr for IS-5-MN and 23.2 l/hr for IS-2-MN. After oral doses the mononitrates were rapidly and completely absorbed (absorption t 1/2 ranged from 2.5 to 5 min) from the gastrointestinal tract without first-pass metabolism, i.e., absolute systemic availability was 100%. In the dose range studied, kinetics of the two mononitrates were linear. Compared with isosorbide dinitrate, mononitrate kinetics are different because of greater systemic availability, slower clearance, and smaller Vd ss.
在两组年轻健康受试者中，静脉注射5毫克异山梨醇5 - 单硝酸酯（IS - 5 - MN）和异山梨醇2 - 单硝酸酯（IS - 2 - MN）以及口服20毫克IS - 2 - MN和10毫克、15毫克及20毫克IS - 5 - MN后，对它们的动力学进行了研究。采用毛细管柱气相色谱法测定单硝酸酯的血浆水平。静脉注射后，IS - 5 - MN和IS - 2 - MN的血浆水平呈双指数下降，可用开放二室模型描述。分布半衰期较快；IS - 5 - MN为8.6分钟，IS - 2 - MN为12.5分钟。物质分布于全身水分中；稳态分布容积（Vd ss），IS - 5 - MN为48升，IS - 2 - MN为55升，消除半衰期IS - 5 - MN为4.15小时，IS - 2 - MN为1.9小时。IS - 5 - MN的总血浆清除率为8.5升/小时，IS - 2 - MN为23.2升/小时。口服给药后，单硝酸酯迅速且完全从胃肠道吸收（吸收半衰期为2.5至5分钟），无首过代谢，即绝对全身可用性为100%。在所研究的剂量范围内，两种单硝酸酯的动力学呈线性。与异山梨醇二硝酸酯相比，单硝酸酯的动力学不同，因为其全身可用性更高、清除率更低且Vd ss更小。
